Uninfected Infants Born to HIV Positive Mothers May Have Impaired Immune Function

	SUMMARY: Infants born to mothers with HIV appear to be more susceptible to certain bacterial infections even if they are not HIV-infected themselves, according to research from South Africa published in the February 9, 2011 Journal of the American Medical Association. HIV-exposed children get fewer antibodies from their mothers through the placenta during gestation, but they show robust responses to vaccination, indicating that their own immune function is not impaired.

Below is the edited text of a press release issued by Imperial College London describing the study and its findings.

Study Suggests Why HIV-Uninfected Babies of Mothers with HIV Might Be More Prone to Infections

Babies whose mothers have HIV, but who are not HIV-infected themselves, are born with lower levels of specific proteins in their blood called antibodies, which fight infection, compared with babies not exposed to HIV, a new study has found. The finding, published today in the Journal of the American Medical Association, might explain in part why uninfected babies born to women with HIV have a higher risk of illness and death early in life.

Major programs using antiretroviral drugs have successfully reduced the rate of mother-to-child transmission of HIV from 20-30 percent to around five percent in some areas of South Africa and to less than one percent in developed countries. However, HIV-uninfected infants born to HIV-infected mothers in Africa are more prone to infections such as pneumonia and meningitis, and up to four times more likely to die before their first birthday, compared with babies born to HIV-negative women. Socioeconomic factors are thought to account partially for this discrepancy but differences in the babies' immune systems might also be important.

The new study, by scientists from Imperial College London and Stellenbosch University in South Africa, found that babies born to HIV-infected mothers had significantly lower levels at birth of antibodies against a range of bacterial infections (Hib, pertussis, pneumococcus and tetanus).

Antibodies, which bind to specific pathogens and direct immune cells to attack them, are transferred from mother to child through the placenta late in pregnancy. The study found lower levels of some specific antibodies in mothers with HIV, but also that less antibody is transferred from mother to child across the placenta.
Despite their low antibody levels at birth, the babies in the study responded well to vaccination: they produced similar levels of antibody to some vaccines and higher levels to other vaccines.

"It's likely that lower antibody levels in these babies contributes to lower protection against infection before the babies have received their vaccines," said Dr Christine Jones from the Department of Pediatrics at Imperial College London, the study's first author. "Although they appear more vulnerable in the first few months of life, the good news is that these babies respond well to vaccination. We might be able to protect them even better against infections, either by vaccinating them earlier or by vaccinating the mother in pregnancy. More research will be needed to establish what the best way of protecting these babies might be."

The study involved 109 HIV-infected and uninfected mothers in a community health centre in Khayelitsha, a rapidly-growing township in Cape Town, South Africa. The researchers measured antibody levels in the mothers at delivery and the infants at birth. They also assessed how the babies responded to routine vaccination by measuring the babies' antibody levels at four months, after they had received their routine vaccines.

Amongst the HIV-negative women in the study, a third also had low antibody levels, showing that protection against infection in their babies might also not be optimal in some women, who are otherwise perfectly healthy.

Dr Beate Kampmann, Reader in Pediatric Infection and Immunity at Imperial and the senior author of the study, said: "Around six million children under five die every year from infectious diseases, and a lot of these deaths are preventable by using existing vaccines. Studies like ours are helping us understand why certain infants might be especially susceptible to infections, and how we might tailor vaccination policies to protect vulnerable babies more effectively."

The Imperial team will soon begin a new project studying antibody levels in babies and mothers with and without HIV, among patient volunteers from Imperial College Healthcare NHS Trust. This work is funded by Imperial's Biomedical Research Centre, which was awarded by the National Institute of Health Research (NIHR).

Investigator affiliations: Academic Department of Pediatrics, Imperial College London, London, UK; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Medical Research Council (UK) The Gambia, Fajara, The Gambia; Department of Pathology, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Services, Tygerberg Hospital, Cape Town, South Africa; Desmond Tutu TB Center, Department of Pediatrics and Child Health, Stellenbosch University, Cape Town, South Africa.